TY - JOUR
T1 - Mesenchymal stem cells induce expression of CD73 in human monocytes in vitro and in a swine model of myocardial infarction in vivo
AU - Monguió-Tortajada, Marta
AU - Roura, Santiago
AU - Gálvez-Montón, Carolina
AU - Franquesa, Marcella
AU - Bayes-Genis, Antoni
AU - Borràs, Francesc E.
PY - 2017/11/20
Y1 - 2017/11/20
N2 - © 2017 Monguió-Tortajada, Roura, Gálvez-Montón, Franquesa, Bayes-Genis and Borràs. The ectoenzymes CD39 and CD73 regulate the purinergic signaling through the hydrolysis of adenosine triphosphate (ATP)/ADP to AMP and to adenosine (Ado), respectively. This shifts the pro-inflammatory milieu induced by extracellular ATP to the anti-inflammatory regulation by Ado. Mesenchymal stem cells (MSCs) have potent immunomodulatory capabilities, including monocyte modulation toward an anti-inflammatory phenotype aiding tissue repair. In vitro, we observed that human cardiac adipose tissue-derived MSCs (cATMSCs) and umbilical cord MSCs similarly polarize monocytes toward a regulatory M2 phenotype, which maintained the expression of CD39 and induced expression of CD73 in a cell contact dependent fashion, correlating with increased functional activity. In addition, the local treatment with porcine cATMSCs using an engineered bioactive graft promoted the in vivo CD73 expression on host monocytes in a swine model of myocardial infarction. Our results suggest the upregulation of ectonucleotidases on MSC-conditioned monocytes as an effective mechanism to amplify the long-lasting immunomodulatory and healing effects of MSCs delivery.
AB - © 2017 Monguió-Tortajada, Roura, Gálvez-Montón, Franquesa, Bayes-Genis and Borràs. The ectoenzymes CD39 and CD73 regulate the purinergic signaling through the hydrolysis of adenosine triphosphate (ATP)/ADP to AMP and to adenosine (Ado), respectively. This shifts the pro-inflammatory milieu induced by extracellular ATP to the anti-inflammatory regulation by Ado. Mesenchymal stem cells (MSCs) have potent immunomodulatory capabilities, including monocyte modulation toward an anti-inflammatory phenotype aiding tissue repair. In vitro, we observed that human cardiac adipose tissue-derived MSCs (cATMSCs) and umbilical cord MSCs similarly polarize monocytes toward a regulatory M2 phenotype, which maintained the expression of CD39 and induced expression of CD73 in a cell contact dependent fashion, correlating with increased functional activity. In addition, the local treatment with porcine cATMSCs using an engineered bioactive graft promoted the in vivo CD73 expression on host monocytes in a swine model of myocardial infarction. Our results suggest the upregulation of ectonucleotidases on MSC-conditioned monocytes as an effective mechanism to amplify the long-lasting immunomodulatory and healing effects of MSCs delivery.
KW - Adenosine
KW - CD73
KW - Ectonucleotidase
KW - Immunomodulation
KW - Mesenchymal stem cell
KW - Myocardial infarction
KW - Purigernic signaling
KW - Regeneration
U2 - 10.3389/fimmu.2017.01577
DO - 10.3389/fimmu.2017.01577
M3 - Article
SN - 1664-3224
VL - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - NOV
M1 - 1577
ER -